12-13087209-A-G

Variant names:

• chr12-13087209-A-G
• NM_001080555.4:c.689T>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001080555.4(GSG1):​c.689T>C​(p.Val230Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V230I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GSG1 NM_001080555.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.42

Genes affected

GSG1 (HGNC:19716): (germ cell associated 1) Predicted to enable RNA polymerase binding activity. Predicted to be located in endoplasmic reticulum membrane. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

FAM234B (HGNC:29288): (family with sequence similarity 234 member B) Predicted to be located in Golgi apparatus and cytoskeleton. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12619284).
• BP6: Variant 12-13087209-A-G is Benign according to our data. Variant chr12-13087209-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3102905.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSG1	NM_001080555.4	c.689T>C	p.Val230Ala	missense_variant	Exon 6 of 7	ENST00000651961.1	NP_001074024.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSG1	ENST00000651961.1	c.689T>C	p.Val230Ala	missense_variant	Exon 6 of 7		NM_001080555.4	ENSP00000498528.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Oct 20, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	8.6
DANN	Benign	0.83
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.58	T;T;T;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.13	T;T;T;T
MetaSVM	Benign	-0.98	T
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-2.1	N;N;N;N
REVEL	Benign	0.057
Sift	Benign	0.52	T;T;T;T
Sift4G	Benign	0.28	T;T;T;T
Polyphen		0.0, 0.0010	.;B;B;B
Vest4		0.31
MVP		0.15
MPC		0.14
ClinPred		0.072	T
GERP RS		-2.3
gMVP		0.19

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-13240143;